Dataset Information

Cilostazol is anti-inflammatory in BV2 microglial cells by inactivating nuclear factor-kappaB and inhibiting mitogen-activated protein kinases.

ABSTRACT:

Background and purpose

Cilostazol is a specific inhibitor of 3'-5'-cyclic adenosine monophosphate (cAMP) phosphodiesterase, which is widely used to treat ischemic symptoms of peripheral vascular disease. Although cilostazol has been shown to exhibit vasodilator properties as well as antiplatelet and anti-inflammatory effects, its cellular mechanism in microglia is unknown. In the present study, we assessed the anti-inflammatory effect of cilostazol on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated murine BV2 microglia.

Experimental approach

We examined the effects of cilostazol on LPS-induced nuclear factor-kappaB (NF-kappaB) activation and phosphorylation of mitogen-activated protein kinases (MAPKs).

Key results

Cilostazol suppressed production of nitric oxide (NO), prostaglandin E(2) (PGE(2)) and the proinflammatory cytokines, interleukin-1 (IL-1), tumour necrosis factor-alpha, and monocyte chemoattractant protein-1 (MCP-1), in a concentration-dependent manner. Inhibitory effects of cilostazol were not affected by treatment with an adenylate cyclase inhibitor, SQ 22536, indicating that these actions of cilostazol were cAMP-independent. Cilostazol significantly inhibited the DNA binding and transcriptional activity of NF-kappaB. Moreover, cilostazol blocked signalling upstream of NF-kappaB activation by inhibiting extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinase (JNK), but without affecting the activity of p38 MAPK.

Conclusion and implications

Our results demonstrate that suppression of the NF-kappaB, ERK, JNK signalling pathways may inhibit LPS-induced NO and PGE(2) production. Therefore, cilostazol may have therapeutic potential for neurodegenerative diseases by inhibiting pro-inflammatory mediators and cytokine production in activated microglia.

SUBMITTER: Jung WK

PROVIDER: S-EPMC2848931 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Publications

Cilostazol is anti-inflammatory in BV2 microglial cells by inactivating nuclear factor-kappaB and inhibiting mitogen-activated protein kinases.

Jung Won-Kyo WK Lee Da-Young DY Park Cheol C Choi Yung Hyun YH Choi Inhak I Park Sae-Gwang SG Seo Su-Kil SK Lee Soo-Woong SW Yea Sung Su SS Ahn Soon-Cheol SC Lee Chang-Min CM Park Won Sun WS Ko Jae-Hong JH Choi Il-Whan IW

British journal of pharmacology 20100128 6

<h4>Background and purpose</h4>Cilostazol is a specific inhibitor of 3'-5'-cyclic adenosine monophosphate (cAMP) phosphodiesterase, which is widely used to treat ischemic symptoms of peripheral vascular disease. Although cilostazol has been shown to exhibit vasodilator properties as well as antiplatelet and anti-inflammatory effects, its cellular mechanism in microglia is unknown. In the present study, we assessed the anti-inflammatory effect of cilostazol on the production of pro-inflammatory m ...[more]

PMID: 20128801

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Dataset Information

Cilostazol is anti-inflammatory in BV2 microglial cells by inactivating nuclear factor-kappaB and inhibiting mitogen-activated protein kinases.

Background and purpose

Experimental approach

Key results

Conclusion and implications

Publications

Cilostazol is anti-inflammatory in BV2 microglial cells by inactivating nuclear factor-kappaB and inhibiting mitogen-activated protein kinases.

Similar Datasets

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